Image_2.jpg
Robert A. LaMothe
Pallavi N. Kolte
Trinh Vo
Joseph D. Ferrari
Tracy C. Gelsinger
Jodie Wong
Victor T. Chan
Sinthia Ahmed
Aditi Srinivasan
Patrick Deitemeyer
Roberto A. Maldonado
Takashi K. Kishimoto
10.3389/fimmu.2018.00281.s002
https://frontiersin.figshare.com/articles/figure/Image_2_jpg/5942695
<p>T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously demonstrated that co-administration of encapsulated or free Ag with tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin are capable of inhibiting Ag-specific transgenic T cell proliferation and inducing Ag-specific regulatory T cells (Tregs). Here, we further show that tNPs can trigger the expansion of endogenous Tregs specific to a target Ag. The proportion of Ag-specific Treg to total Ag-specific T cells remains constant even after subsequent Ag challenge in combination with a potent TLR7/8 agonist or complete Freund’s adjuvant. tNP-treated mice do not develop experimental autoimmune encephalomyelitis (EAE) after adoptive transfer of encephalitogenic T cells; furthermore, tNP treatment provided therapeutic protection in relapsing EAE that was transferred to naïve animals. These findings describe a potent therapy to expand Ag-specific Tregs in vivo and suppress T cell-mediated autoimmunity.</p>
2018-03-02 04:18:25
nanoparticles
immunological tolerance
rapamycin
regulatory T cells
experimental autoimmune encephalomyelitis